Table 2.
Studies of reprogramming age-related epigenetic changes.
| Reprogramming method | Model | Main findings | References |
|---|---|---|---|
| OSKM retrovirus transduction | Mouse fibroblasts | Induction of pluripotent stem cells possible with these four transcription factors. Epigenetics not explored. | (Takahashi and Yamanaka 2006) |
| OSK/OSKM retrovirus transduction | Mouse fibroblasts | Induction of pluripotent stem cells possible - telomeres elongated and have same histone marks as young embryonic stem cells | (Marion et al. 2009) |
| OSKM retrovirus transduction | Aged mouse hematopoietic stem cells | Induction of pluripotent stem cells possible - reset telomere length and gene expression profiles. | (Wahlestedt et al. 2013) |
| OSKMNL/OSKM retrovirus transduction | Human senescent and centenarian fibroblasts | Induction of pluripotent stem cells possible - reset telomere length and gene expression profiles. Epigenetics not explored. | (Lapasset et al. 2011; Yagi et al. 2012) |
| OSKM retrovirus transduction | HGPS patient fibroblasts | Induction of pluripotent stem cells possible - prevented progerin accumulation and reset histone marks eg. H3K9me3 | (Liu et al. 2011) |
| OSKM retrovirus transduction or trans-differentiation | Aging human fibroblasts | Reprogrammed fibroblasts that were differentiated into neurons had no genetic/epigenetic marker of aging. | (Mertens et al. 2018) |
| OSKM retrovirus transduction | Human bone marrow-derived mesenchymal stromal cells and fibroblasts | OSKM induction reset the Horvath DNA methylation epigenetic clock to that of embryonic stem cells. | (Horvath 2013) |
| Inducible OSKM model | Mice | Induction of pluripotent stem cells as indicated by Nanog marker found in many tissues. High mortality from teratomas. | (Abad et al. 2013; Ohnishi et al. 2014) |
| Injection of OSKM plasmids | Mice | Reprogramming markers detected in 24–48 hours, no teratoma evidence. | (Yilmazer et al. 2013) |
| Skeletal muscle injection of OSKM plasmids | Mice | Upregulated pluripotency markers, and improved regeneration potential | (de Lázaro et al. 2017) |
| Inducible OSKM model | Mouse HGPS model (LAKI 4F mice) | Cyclic in vivo induction of factors, restored normal levels of H3K9me3, and H4K20me3, and increased muscle injury recovery and other aging phenotypes | (Ocampo et al. 2016) |
| OSKM | Naked mole rats | Resistant to reprogramming with OSKM as more stable epigenome than mice. | (Tan et al. 2017) |